To analyze the possible H-2 restriction of the sensitization phase of contact hypersensitivity, murine skin will be painted with DNFB and grafted onto syngeneic and allogeneic hosts. Five days later, these recipients will be ear-challenged with DNFB. The role of graft adaptation in neonatal tolerance of H-2 transplantation alloantigens will be studied to determine whether this mechanism is operational in the long-term acceptance of H-2 disparate skin grafts. We have shown that long-term primed responder murine cell lines specifically recognize xenogeneic hamster determinants. We plan to analyze the fine specificity of this proliferative response, using T-cell clones generated by the limiting dilution method. The humoral and cellular immune responses of female rats have been assessed following pregnancy. With increasing parity, rejection of paternal allografts is increasingly impaired. This hyporesponsiveness is specific for paternal antigens, influenced by exposure to sperm and trophoblast, and arises at day 12 of pregnancy. Further investigation will define the role of fetal cells escaping across the placenta and the uterine exposure site and the extensive maternal decidua that develops. It has been suggested that the reproductive efficiency of MHC-compatible pregnancies is less than that of MHC-incompatible pregnancies. To test this hypothesis, we will use the following parameters in rats to compare the efficiency of MHC-compatible (DA-female times ACI-male, ACI-female times DA-male) and MHC-incompatible (DA-female times FI-male, ACI-female times-FI male) pregnancies: 1) percentage of animals that mate; 2) number of pregnancies resulting; and 3) litter size, number born dead.